Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

DOI record: { "DOI": "10.3390/microorganisms10061118", "ISSN": [ "2076-2607" ], "URL": "http://dx.doi.org/10.3390/microorganisms10061118", "abstract": "<jats:p>The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p &gt; 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p &lt; 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI 1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.</jats:p>", "alternative-id": [ "microorganisms10061118" ], "author": [ { "affiliation": [], "family": "Delić", "given": "Nikola", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0001-9272-6906", "affiliation": [], "authenticated-orcid": false, "family": "Matetic", "given": "Andrija", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-7003-8192", "affiliation": [], "authenticated-orcid": false, "family": "Domjanović", "given": "Josipa", "sequence": "additional" }, { "affiliation": [], "family": "Kljaković-Gašpić", "given": "Toni", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5621-580X", "affiliation": [], "authenticated-orcid": false, "family": "Šarić", "given": "Lenko", "sequence": "additional" }, { "affiliation": [], "family": "Ilić", "given": "Darko", "sequence": "additional" }, { "affiliation": [], "family": "Došenović", "given": "Svjetlana", "sequence": "additional" }, { "affiliation": [], "family": "Domazet", "given": "Josipa", "sequence": "additional" }, { "affiliation": [], "family": "Kovač", "given": "Ruben", "sequence": "additional" }, { "affiliation": [], "family": "Runjić", "given": "Frane", "sequence": "additional" }, { "affiliation": [], "family": "Stipić", "given": "Sanda Stojanović", "sequence": "additional" }, { "affiliation": [], "family": "Duplančić", "given": "Božidar", "sequence": "additional" } ], "container-title": "Microorganisms", "container-title-short": "Microorganisms", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2022, 5, 30 ] ], "date-time": "2022-05-30T03:43:03Z", "timestamp": 1653882183000 }, "deposited": { "date-parts": [ [ 2022, 5, 30 ] ], "date-time": "2022-05-30T04:00:51Z", "timestamp": 1653883251000 }, "indexed": { "date-parts": [ [ 2022, 5, 30 ] ], "date-time": "2022-05-30T04:42:53Z", "timestamp": 1653885773518 }, "is-referenced-by-count": 0, "issue": "6", "issued": { "date-parts": [ [ 2022, 5, 28 ] ] }, "journal-issue": { "issue": "6", "published-online": { "date-parts": [ [ 2022, 6 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 5, 28 ] ], "date-time": "2022-05-28T00:00:00Z", "timestamp": 1653696000000 } } ], "link": [ { "URL": "https://www.mdpi.com/2076-2607/10/6/1118/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "1118", "prefix": "10.3390", "published": { "date-parts": [ [ 2022, 5, 28 ] ] }, "published-online": { "date-parts": [ [ 2022, 5, 28 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1001/jama.2020.2648", "doi-asserted-by": "publisher", "key": "ref1" }, { "key": "ref2" }, { "DOI": "10.3390/antibiotics10050545", "doi-asserted-by": "publisher", "key": "ref3" }, { "DOI": "10.1097/CCM.0b013e3182281f33", "doi-asserted-by": "publisher", "key": "ref4" }, { "DOI": "10.1097/MCC.0000000000000908", "doi-asserted-by": "publisher", "key": "ref5" }, { "DOI": "10.1080/17476348.2017.1359090", "doi-asserted-by": "publisher", "key": "ref6" }, { "DOI": "10.1007/s40261-019-00861-x", "doi-asserted-by": "publisher", "key": "ref7" }, { "article-title": "Evaluation of the Effect of Nebulized N-Acetylcysteine on Respiratory Secretions in Mechanically Ventilated Patients: Randomized Clinical Trial", "author": "Masoompour", "first-page": "309", "journal-title": "Iran. 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